Abstract
Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adipocytes / metabolism*
-
Adipose Tissue, Brown / cytology*
-
Adipose Tissue, Brown / ultrastructure
-
Animals
-
Energy Metabolism / physiology*
-
Gene Expression Regulation*
-
Genes, Reporter
-
HeLa Cells
-
Humans
-
Lipids / analysis
-
Liver / cytology
-
Mice
-
Mutagenesis, Site-Directed
-
Obesity / genetics
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
-
Promoter Regions, Genetic
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Receptors, Cytoplasmic and Nuclear / deficiency
-
Receptors, Cytoplasmic and Nuclear / genetics
-
Receptors, Cytoplasmic and Nuclear / metabolism*
-
Receptors, Estrogen / metabolism
-
Thermogenesis / genetics
-
Thermogenesis / physiology
-
Trans-Activators / genetics*
-
Trans-Activators / metabolism
-
Transcription Factors
-
Transcriptional Activation
Substances
-
Lipids
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
-
Ppargc1a protein, mouse
-
RNA, Messenger
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Estrogen
-
Trans-Activators
-
Transcription Factors
-
nuclear receptor subfamily 0, group B, member 2